A number of inflammatory and neoplastic diseases of the eye are now treated by systemic drug therapy. Unfortunately, the majority of these drugs are associated with numerous systemic side-effects. We are developing sustained drug release devices for intraocular implantation that could release drugs for periods as long as five years. These would eliminate the need for systemic therapy, avoid the invasiveness of direct intravitreal injection, and improve drug compliance. A number of different drugs and device configurations are being designed and evaluated by means of in vitro and in vivo methods. We are developing mathematical models that incorporate the geometry and physical properties of the device, physico-chemical properties of the drug, pharmacokinetics of drug clearance, and physiology of the eye to assist in design of the devices. The methodology was applied to the anti- inflammatory drug leflunomide. In vivo studies demonstrated that a silicone-coated drug pellet releasing drug at a constant rate could produce therapeutic concentrations of the active metabolite for at least three months when implanted in the vitreal cavity. Mathematical analysis suggests that the device provides a >30-fold pharmacokinetic advantage over systemic dosing. The methodology is being explored with other drugs for treatment of a wide variety of chronic eye diseases such as macular degeneration. - intraocular implant, controlled drug delivery, mathematical model, polymer